Multiomics Analyses Reveal the Central Role of Pentose Phosphate Pathway in Resident Thymic Macrophages to Cope with Efferocytosis-Associated Stress
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ABSTRACT: Tissue-resident macrophages (TRMs) are heterogeneous cell populations found throughout the body. Depending on their location, they perform diverse functions maintaining tissue homeostasis and providing immune surveillance. To survive and function within, TRMs adapt metabolically to the distinct microenvironments. However, little is known about the metabolic signatures of TRMs. The thymus provides a nurturing milieu for developing thymocytes yet efficiently removes those that failed the selection, relying on the TRMs – resident thymic macrophages (TMφs). This study harnesses multiomics analyses to characterize TMφs and unveils their unique metabolic features. We find that the pentose phosphate pathway (PPP) is preferentially activated in TMφs, responding to the reduction-oxidation demands associated with the efferocytosis of dying thymocytes. The blockade of PPP in Mφs leads to decreased efferocytosis, which can be rescued by ROS scavengers. Our study reveals the key role of PPP in TMφs and underscores the importance of metabolic adaptation in supporting Mφ efferocytosis.
ORGANISM(S): Mouse Mus Musculus
TISSUE(S): Macrophages
SUBMITTER: Chia-Lin Hsu
PROVIDER: ST002177 | MetabolomicsWorkbench | Sat May 21 00:00:00 BST 2022
REPOSITORIES: MetabolomicsWorkbench
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